This new research proposal is concerned with the molecular mechanisms involved in the expression and transcriptional control of drug resistance genes carried by an extrachromosomal genetic element, R plasmid(R factor), present in drug resistant bacteria. Since the discovery of R plasmid over a decade ago, R plasmids have been widespread in geographical distribution and also in wide variety of pathogenic and nonpathogenic bacteria. Incidents of R plasmid- determined antibiotic resistance, often multi-resistance, are increasing and causing a serious problem in human and veterinary medicine. It is now well established that the antibiotic resistance of a bacterium carrying R plasmid is due to a production of an R plasmid- coded enzyme which modifies and inactivates the target antibiotic. However, due to the lack of comprehensive studies on the transcription of R plasmid genes in general, no detailed information is available for the control of R plasmid gene expression. Therefore, we have decided to undertake a research on the control of R plasmid gene expression utilizing our experience in studying transcriptional and translational control of bacteriophage gene expression. Our major objectives are: 1. Comprehensive characterization of transcriptional processes and transcripts of R plasmid genes in vivo and in vitro. 2. Transcriptional control of R plasmid gene expression with special attention to the catabolite repression at the transcriptional level. 3. Multi-copy R plasmid DNA replication in relation to the degree of drug resistance in order to determine whether the gene dose effect is involved in the increase of drug resistance of the host bacteria in addition to transcriptional control of the drug resistance genes.